Hepatic fibrosis is a significant cause of morbidity and mortality worldwide. Fibrosis can be characterized as an exacerbated wound-healing response to chronic injury, and if unresolved, may proceed to cirrhosis. A variety of hepatic insults, namely chronic ethanol consumption, can lead to development of fibrosis/cirrhosis. The hepatic stellate cell (HSC) is considered the main effector cell in liver fibrosis as it produces excessive amounts of collagen scar matrix leading to organ dysfunction. Transforming growth factor beta (TGF) is the most potent profibrogenic molecule stimulating HSC activation and subsequently collagen deposition. Currently, there are no FDA-approved treatments for liver fibrosis/cirrhosis, and liver transplant remains the only cure for cirrhosis. Recent attention has been focused on the regulatory role of microRNAs (miRs) in liver disease pathology, and they show great potential for therapeutic strategies in management of hepatic fibrosis. Specifically, we demonstrated miR19b is significantly decreased in HSCs from fibrotic rat and human liver compared to normal tissue. Mechanistically, overexpression of miR19b inhibits Transforming Growth Factor beta (TGF) signaling and subsequent collagen production and activation of the HSC via direct binding to the 3'UTR of TGF Receptor II mRNA. Overall, establishing treatments for fibrosis/cirrhosis will decrease yearly deaths and US economic burden. Therefore, the current application will address the following specific aims: 1) establish cellular mechanisms regulating miR19b biogenesis in the HSC which will lay the foundation for future means of manipulating endogenous expression in vivo, and 2) test miR19b as an effective anti-fibrotic treatment in vivo.